Matsubara H, Hirata Y, Yoshimi H, Takata S, Takagi Y, Umeda Y, Yamane Y, Inada M
Hypertension-Endocrine Division, National Cardiovascular Center Research Institute, Osaka, Japan.
Am J Physiol. 1988 Sep;255(3 Pt 2):H405-9. doi: 10.1152/ajpheart.1988.255.3.H405.
The secretory mechanism of rat atrial natriuretic peptide (rANP) was studied in vitro with the use of primary culture of atrial myocytes from neonatal rats. Norepinephrine, phenylephrine, and carbamylcholine stimulated immunoreactive (IR) rANP secretion, whereas neither angiotensin II, arginine vasopressin, nor isoproterenol affected its secretion. The stimulatory effects of carbamylcholine and phenylephrine were blocked by atropine and prazosin, respectively. 12-O-tetradecanoylphorbol-beta-acetate (TPA), protein kinase C activator, induced a dose-dependent increase in IR rANP secretion, and TPA combined with Ca2+ ionophore ionomycin produced a synergistic effect. Ca2+-channel agonist BAY K 8644 also stimulated IR rANP secretion, the effect of which was blocked by Ca2+-channel antagonist nifedipine. These data suggest that alpha 1-adrenergic and muscarinic cholinergic agonists have direct action on rat cardiocytes to stimulate ANP secretion that involves receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C.
利用新生大鼠心房肌细胞原代培养物在体外研究了大鼠心房利钠肽(rANP)的分泌机制。去甲肾上腺素、苯肾上腺素和卡巴胆碱刺激免疫反应性(IR)rANP分泌,而血管紧张素II、精氨酸加压素和异丙肾上腺素均不影响其分泌。卡巴胆碱和苯肾上腺素的刺激作用分别被阿托品和哌唑嗪阻断。蛋白激酶C激活剂12 - O - 十四酰佛波醇 - β - 乙酸酯(TPA)诱导IR rANP分泌呈剂量依赖性增加,TPA与Ca2 +离子载体离子霉素联合产生协同效应。Ca2 +通道激动剂BAY K 8644也刺激IR rANP分泌,其作用被Ca2 +通道拮抗剂硝苯地平阻断。这些数据表明,α1 - 肾上腺素能和毒蕈碱胆碱能激动剂对大鼠心肌细胞有直接作用,可刺激ANP分泌,这涉及受体介导的细胞内Ca2 +动员和蛋白激酶C的激活。